PB1755: CASPASE 8, CASPASE 10 AND FAS GENE POLYMORPHISMS IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: M. Lourou, E. Kampouraki, M. Zervou, I. Pelagiadis, N. Katzilakis, G. Goulielmos, E. Stiakaki
Journal: HemaSphere (2022)

Background: Acute lymphoblastic leukemia (ALL) is the most common type of childhood leukemia accounting for one third of all pediatric malignancies. Over the last decade major progress has been made in understanding the biology of ALL, genetic basis of leukemogenesis and response to treatment. Epidemiological studies have shown that various genetic factors play a crucial role in leukemogenesis. Abnormal regulation of apoptosis and the deregulation of expression or function of caspase antagonists’ pathways seem to play an important role in the pathogenesis and progression of hematological malignancies. Polymorphisms in the apoptotic genes may enhance the risk of disease, as implicated by the strong link between genetic diversity and susceptibility to ALL. Caspases are a family of cysteine proteases whose functions are strongly associated with programmed cell death. Caspase 8 plays an important role in apoptosis and several studies have been performed to clarify the relationship between polymorphisms in Casp8 gene and different types of cancer. Caspase 10 is the only caspase that shares homologous death–effector domains with Caspase 8, while somatic mutations in Casp10 gene have been observed in many cancers. Fas is a transmembrane molecule belonging to the tumor necrosis factor (TNF) receptor superfamily and its ligation by FasL induces programmed cell death in several lymphoid cell lines. Studies suggest that polymorphisms in the FAS gene may affect cancer risk. Aims: The purpose of this study was the investigation of the incidence of rs1045485 single nucleotide polymorphism (SNP), located in exon 10 of the Casp8 gene, rs13006529 SNP, located in exon 10 of the Casp10 gene and rs2234767 SNP, located in the promoter of FAS gene, in children and adolescents with ALL, compared to healthy individuals. Methods: The patient group consisted of 119 children and adolescents (1 to 18 years) with ALL and the control group of 121 healthy individuals. The genomic DNA was isolated from the peripheral blood or the bone marrow and the genetic regions harboring the SNPs under investigation were amplified with Polymerase Chain Reaction (PCR). The PCR product was subsequently digested with the appropriate restriction enzymes (BstUI for rs1045485 and rs2234767, SspI for rs13006529). Statistical analysis was performed with GraphPad Prism application (GraphPad Software, San Diego, CA, USA). Results: The frequencies of the minor alleles of rs1045485, rs13006529 and rs2234767 SNPs of Casp8, Casp10 and FAS genes, respectively, were significantly increased in ALL patients compared to controls. In particular, there was an association between ALL diagnosis and the aforementioned alleles of these three genes studied (G for Casp8, T for Casp10, G for FAS). Likewise, both the homozygotes for the minor alleles as well as the heterozygotes (CG/GG for Casp8, AT/TT for Casp10 and AG/GG for FAS) were associated with ALL in children and adolescents (Table 1). Image:Summary/Conclusion: Rs1045485, rs13006529 and rs2234767 SNPs of Casp8, Casp10 and FAS genes, respectively, were strongly associated with the diagnosis of ALL in the studied population. Further investigation would be of great interest in an attempt to clarify the functional role of these polymorphisms in the development of the disease.